Posts tagged 𔃴-1BB’

Despite remarkable results with cancer immunotherapy to date, we do need to keep out feet on the ground and remember that response rates are relatively low to modest (10–30%) and the majority of patients do not respond or see a benefit with these approaches.

As we start moving beyond checkpoint monotherapy, the realisation has fast hit many researchers and companies that we really don’t know as much about the tumour microenvironment (TME) as we would like.

No doubt we will learn a lot more about it from the combinatory approaches, but be aware that this also means higher risk associated with such developments – we will likely see a lot of failures – and hopefully, some successes too.

This is where the little biotech companies have an opportunity to shine… they may have some intriguing IO compounds in development but not an anti-PD1/L1 backbone, meaning they can collaborate with a big pharma company to explore novel combinations in small phase 1/2 trials to determine what works or not. This is much lower risk (and R&D costs) for both parties and we get to see more quickly where things shake out.

At the annual Society for Immunotherapy of Cancer (SITC) meeting last week, there was a whole day devoted to New Immunotherapy Drug Development.

Some of these agents look worthy of watching out for and following their progress. A variety of data in different targets and MOA were presented from big and small companies alike. We selected a few of the promising ones for further review and discussion.

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We’ve come a long way over the last two years in the oncology market, with several novel approaches approved, numerous major phase 3 trials evolving and a huge turnaround for many companies in terms of early pipeline activity.

The melée at the ASCO 2016 Poster Hall

Unfortunately, this also means that the tendency of lemming activity also increases in the rush to copy everyone else and not be left behind. Just a couple of years ago, some industry friends grumbled that there were over 20 checkpoint inhibitors chasing them in development; they may be surprised to know that now there are nearly 70! This is both unprecedented and unsustainable, and yet it’s also a function of the perceived success these agents have had on the cancer R&D landscape to date. Everyone wants one for fear of being left behind… except that many are indeed way behind already.

You can imagine the tall guy on the left of the picture looking at his watch and wondering, “Ah so many new posters, so little time!”

Meanwhile, as the rate of approved cancer therapies increases, so does the inexorable march in terms of hyper-aggressive basket pricing. I would argue that at some point, it no longer acceptable or even conscionable to change a premium or even market rate for drugs that give an incremental improvement of a mere 2 months of extra life.

Equally, one thing that many industry observers and the media love to do, and wrongly in my view, is to compare the individual drug prices on an annualized basis. This is silly for several reasons:

So far, not all patients are treated for a full year

If patients are treated until progression and that happens early, then therapy is stopped

What people should be looking at is the average treatment cost based on the length of therapy – some people will receive a few months and some much more than that

What’s the true cost of a cure or remission to a patient and their family?

How do we quantify the impact of the long lasting durable remissions?

These questions will become increasingly important as we see a more aggregated therapy approach emerge over the next few years.

By this, I mean that we are now going beyond monotherapy and even combinations; those trials have already long started and are the low hanging fruit that has been rapidly snapped up by the early players, as we eagerly wait for their data readouts.

If you have new agents coming-out of preclinical and into phase 1 development over the next year, there are a number of important questions to consider:

What are you going to do and where do you start?

How do you gain an edge when coming from (way) behind?

How do you develop unique positioning that could sustain your molecule in a sea of similar competitors?

Is it realistic to expect the 17th and 50th checkpoint to have equivalent efficacy as what went on before and will all of these seriously make it to market?

You can see now why even the FDA’s Dr Richard Pazdur was moved to grumble about the surfeit of me-toos here and company expectations that the FDA should consider them – it’s on a massive scale that we haven’t seen before. For once I agree and empathize with him over that dilemma, it’s madness to think they will all be as good as pembrolizumab or nivolumab.

What we are starting to see emerge now is a surprising synthesis of ideas and a merging of disparate approaches. How will this affect oncology R&D over the next 1–5 years?

A couple of smart readers wrote in asking about these emerging trends, what have we identified so far, and where do we see the oncology space going in the near to medium term future. Now that AACR and ASCO are behind us, what can we learn about the new developments and where they all fit in the oncology landscape strategically?

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Lung cancer, along with metastatic melanoma, has been very much to the forefront of attention in cancer immunotherapies with both nivolumab (Opdivo) and pembrolizumab (Keytruda) garnering approval as monotherapy from the FDA in second line treatment of NSCLC. A third molecule, atezolizumab (Tecentriq) has also been submitted to the authorities for this indication and a decision is expected soon.

Street art in the Chicago West Loop

While no one is in any doubt that the response rates with monotherapy are low (in the 20% range) and the majority of people do not respond, the important thing so far is that when they do, they appear to be very durable responses. People are living longer, much longer than the 2–3 months of incremental improvement we are used to seeing with chemotherapy or targeted therapies.

The race is now on to see how we can improve things for the 80% of people with lung cancer who don’t respond to single agent therapy:

What can we do to help them?

Which combinations look more encouraging?

Should we treat beyond progression?

To answer these questions, we interviewed Dr Stephen Liu and discussed his views on some of the cancer immunotherapy combination studies presented at ASCO last week.

Dr Stephen Liu at ASCO 2016

Dr Liu is a lung cancer expert at the Lombardi Cancer Centre at Georgetown University, and is actively involved in numerous clinical trials, particularly in Developmental Therapeutics.

Georgetown’s founding principle is Cura Personalis, which translates as care of the whole person. It “suggests individualized attention to the needs of others, distinct respect for unique circumstances and concerns, and an appropriate appreciation for singular gifts and insights.”

Dr Liu embodies this ideal, advocating for his patients for access to the best research advances, including genomics and clinical trials of promising agents. At ASCO, he kindly highlighted some of the important findings from Chicago and offered context on why they matter to the field.

He told us one combination was “potentially transformative” and could be “practice changing” in lung cancer with more data.

Intrigued? To find out what these important trials are and which ones to watch out for, subscribers can log-in to read the article or you can sign-up by clicking on the Blue Box below.

Spring has arrived in many parts of the world, and with it I am always reminded of William Wordsworth’s classic poem, “I Wandered Lonely as a Cloud:”

I wandered lonely as a cloud

That floats on high o’er vales and hills,

When all at once I saw a crowd,

A host, of golden daffodils;

Beside the lake, beneath the trees,

Fluttering and dancing in the breeze.

So what does the future hold for cancer immunotherapy?

Inspired by Wordsworth, I’ve sat on my cloud and have looked at some of the recent review papers and thought pieces published by experts in the field. Do they offer a Jerry Maguire – like mission statement: “The Things We Think and Do Not Say: The Future of Our Business” or will we have to wait till AACR 2016 in New Orleans to learn more?

This is the latest in our pre-AACR 2016 annual meeting series. Subscribers can login to read more or you can purchase access below.

At the forum, Dr Sznol also led a breakout session, where he reviewed what is melanoma, the treatment of primary melanoma and management of advanced disease, as well as answering questions from the patients and patient advocates.

Often at medical meetings you hear the results of a clinical trial that is but one piece of the jigsaw, so it was interesting to hear a more comprehensive overview of the disease.

Dr Sznol kindly spoke with BSB about his vision for the future of cancer immunotherapies. This post includes excerpts from the interview along with additional commentary.

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Greetings from Vienna where we are gearing up for our coverage of the European Cancer Congress (Twitter #ECC2015).

We’ll be writing a “highlights” post for subscribers at the end of the day here on Saturday, Sunday and Monday, then will follow- up with more in-depth coverage after we have talked with experts about the data presented.

Checkpoint Inhibitors and Cancer Immunotherapy are not surprisingly hot topics at the meeting.

In case you missed it, this month’s episode of Novel Targets (are we really on show #6 already?!) takes us on a new branch of the journey looking at various aspects of cancer immunotherapy:

Boosting T cell production – Stepping on the Gas

In past shows, we’ve looked at unlocking the brakes (checkpoint inhibitors), immune biomarkers (MDSCs and STING pathway), an inflamed or immunologic tumour type (lung cancer), a non-inflamed tumour type (prostate cancer), adoptive cell therapies and now it’s time for something really different… what happens when we literally step on the gas with immune agonists?